Glandular Distribution Research Articles

THUBreast: an open-source breast phantom generation software for x-ray imaging and dosimetry

Objective. Establishing realistic phantoms of human anatomy is a continuing concern within virtual clinical trials of breast x-ray imaging. However, little attention has been paid to glandular distribution within these phantoms. The principal objective of this study was to develop breast phantoms considering the clinical glandular distribution. Approach. This research introduces an innovative method for integrating glandular distribution information into breast phantoms. We have developed an open-source software, THUBreast 4 4 http://github.com/true02Hydrogen/THUBreast/ , which generates breast phantoms that accurately replicate both the structural texture and glandular distribution, two crucial elements in breast x-ray imaging and dosimetry. To validate the efficacy of THUBreast, we assembled three groups of breast phantoms (THUBreast, patient-based, homogeneous) for irradiation simulation and calculated the power-law exponents ( β ) and mean glandular dose ( Dg ), indicators of texture realism and radiation risk, respectively, utilizing MC-GPU. Main results. Upon the computation of the Dg for the THUBreast phantoms, it was found to be in agreement with that absorbed by the phantoms based on patients, with an average deviation of 4%. The estimates of average Dg thus obtained were on average 23% less than those computed for the homogeneous phantoms. It was observed that the homogeneous phantoms did overestimate the average Dg by 30% when compared to the phantoms based on patients. The mean value of β for the images of THUBreast phantoms was found to be 2.92 ± 0.08, which shows a commendable agreement with the findings of prior investigations. Significance. It is evidently clear from the results that THUBreast phantoms have a preliminary good performance in both imaging and dosimetry in terms of indicators of texture realism and glandular dose. THUBreast represents a further step towards developing a powerful toolkit for comprehensive evaluation of image quality and radiation risk.

A voxel-by-voxel method for mixing two filaments during a 3D printing process for soft-tissue replication in an anthropomorphic breast phantom

Objective. In this study, a novel voxel-by-voxel mixing method is presented, according to which two filaments of different material are combined during the three dimensional (3D) printing process. Approach. In our approach, two types of filaments were used for the replication of soft-tissues, a polylactic acid (PLA) filament and a polypropylene (PP) filament. A custom-made software was used, while a series of breast patient CT scan images were directly associated to the 3D printing process. Each phantom´s layer was printed twice, once with the PLA filament and a second time with the PP filament. For each material, the filament extrusion rate was controlled voxel-by-voxel and was based on the Hounsfield units (HU) of the imported CT images. The phantom was scanned at clinical CT, breast tomosynthesis and micro CT facilities, as the major processing was performed on data from the CT. A side by side comparison between patient´s and phantom´s CT slices by means of profile and histogram comparison was accomplished. Further, in case of profile comparison, the Pearson´s coefficients were calculated. Main results. The visual assessment of the distribution of the glandular tissue in the CT slices of the printed breast anatomy showed high degree of radiological similarity to the corresponding patient´s glandular distribution. The profile plots´ comparison showed that the HU of the replicated and original patient soft tissues match adequately. In overall, the Pearson´s coefficients were above 0.91, suggesting a close match of the CT images of the phantom with those of the patient. The overall HU were close in terms of HU ranges. The HU mean, median and standard deviation of the original and the phantom CT slices were −149, −167, ±65 and −121, −130, ±91, respectively. Significance. The results suggest that the proposed methodology is appropriate for manufacturing of anthropomorphic soft tissue phantoms for x-ray imaging and dosimetry purposes, since it may offer an accurate replication of these tissues.

Anatomical, Histological and Radiological Studies of Parotid Salivary Glands of the Red Fox (Vulpes vulpes) with Comparison to Baladi Dog

The present study was designed to investigate and compare the gross anatomy and histology of the parotid glands, with details of their ducts and radicals, in dogs and foxes, using contrast radiographs. It was applied on six heads for each apparently healthy, adult Baladi dog and red fox that was euthanatized by pentobarbital. All parotid salivary glands were dissected for morphological investigations. Two specimens were injected through the parotid papilla by colored latex neoprene to show the intra glandular distribution of the parotid duct and the other one was inoculated by Urographin for lateral radiograph. The parotid salivary gland appeared as a thin, unevenly triangular shaped gland, located ventrally to the base of the ear. Dorsal border of the gland was notched in the dog but not in the red fox. The parotid radicals had four main branches in the dog, while three major radicals were seen in red fox. Portions of the right and left lobes of parotid salivary glands from other three heads for each dog and fox were fixed in 10% neutral buffered formalin for histological and histochemical investigation. The parotid gland of the dog consisted of pure serous acini, while it consisted of both serous and mucous secretory units in the fox. The acinar cells in the dog revealed a weak positive reaction to the Alcian blue stain. On the contrary, acinar cells in the fox were particularly mucous adenomeres, displaying a significantly high positive reaction. Both secretory acinar cells and duct system lining cells in the dog and fox parotid gland showed weak positive reaction to Periodic Acid-Schiff stain. This work gave a detailed description of parotid salivary gland to help veterinarians in clinical diagnosis and surgical approach.

GATE/GEANT4 simulation of radiation risk induced cancer from mammographic screening

The main objective of the paper is to estimate organ risk of radiation-induced cancer using Monte Carlo simulation Gate/Geant4 applying the Moroccan breast screening guidelines using digital mammography (DM) technique taken into consideration two views (cranio-caudal (CC) and medio-lateral oblique (MLO)), considering the age range of 45–60 years. We apply a new approach consisting of the use of a female voxel phantom EVA and FASH 3 computational phantoms merged with three-layer heterogeneous mammographic phantoms to estimate the incidence risks of cancer on a particular organ and the calculation of the total effective risk of radiation-induced cancer. The effective risk (ER) discrepancy between standing posture phantom FASH 3 and supine posture EVA phantom for organs were: 29.9% (breast examined), 54.83% (thyroid), and 10.97% (total effective risk). These results show a posture sensitivity in terms of organ dose calculation. To investigate the impact of glandular distribution on the ER, each layer of the breast was set to a glandular fraction of 25%, 50%, or 75% to simulate a glandular heterogeneous distribution of uniform, concentrated, superior, and inferior glandular distributions. The heterogeneous distribution shows lower values of the total effective risk of radiation-induced cancer of those of uniform one. This finding shows that the total effective risk for radiation-induced cancer using voxel phantom and heterogeneous breast distribution should be considered in clinical practice to provide DRL in conventional breast dosimetry.

Abstract NG15: Investigation of relationships between breast cancer risk factors and bilateral mammographic breast density asymmetry among women undergoing diagnostic image-guided breast biopsies

Introduction: The etiology of breast cancer remains an area of ongoing investigation. Improving our understanding of factors associated with breast cancer development will strengthen the utility of risk prediction strategies and improve risk stratification. Mammographic breast density remains one of the most influential breast cancer risk factors, with 4 to 6 fold elevated risk observed among women with the highest compared to the lowest levels. These associations have consistently been observed irrespective of the method (visual or automated), used to quantify breast density, showing the robustness of the associations. An understudied breast cancer risk factor is the bilateral asymmetry of mammographic features, with prior studies suggesting that women with higher levels of breast asymmetry may be at elevated breast cancer risk. Increasingly, studies are recognizing the potential of bilateral breast asymmetry defined by mammographic breast density in determining breast cancer risk. Recently, Eriksson and colleagues highlighted a strong influence of breast asymmetry within a model they developed to predict short-term breast cancer risk among women attending breast screening. They observed that the contribution to the model of asymmetry in mammographic breast density, microcalcifications, and masses between the breasts was as substantial as the total number of microcalcifications and masses found within a mammogram, indicating that differences between the breasts may be an important risk marker. To help further understand associations between breast cancer risk factors and asymmetry of breast density, particularly among women at elevated risk for breast cancer, we evaluated risk factor relationships with the bilateral asymmetry of volumetric measures of global and local breast density across the spectrum of premalignant and invasive breast cancer diagnoses. Methods: This study included 882 women enrolled as part of the National Cancer Institute9s Breast Radiology Evaluation and Study of Tissues (BREAST)-Stamp Project (2007-2010). The BREAST-Stamp Project is a cross-sectional molecular epidemiologic study that aims to understand how novel breast density measures are related to breast cancer etiology. Women were enrolled if they were referred for diagnostic image-guided breast biopsy following an abnormal mammogram at the University of Vermont Medical Center, and had not previously been diagnosed or treated for cancer, undergone breast surgery within one year or received chemoprevention. Risk factor data were collected at study enrolment via interview and self-administered questionnaires. Breast density measures were estimated using Single X-ray Absorptiometry (SXA), a technique in which an SXA breast density phantom was affixed to the compression paddle of the mammography machine during routine mammography so that it was included in the X-ray field. It served as a reference standard to estimate volumetric breast density. Breast density was assessed using pre-biopsy craniocaudal full-field digital mammograms of both the ipsilateral (affected) and contralateral (unaffected) breast. Firstly, global density from each laterality was determined as percent fibroglandular volume (%FGV). Secondly, localized volumetric density measures were estimated following identification of the biopsy site on the ipsilateral pre-biopsy mammogram by the study radiologist and identifying the corresponding site on the contralateral mammogram. The SXA estimated %FGV in a perilesional volume twice the size of, but excluding, the biopsy target, centered at the biopsy site. Previous estimates of reproducibility for the SXA test phantoms demonstrated a repeatability SD of 2%, with a ±2% accuracy for the entire thickness and density ranges. Breast density asymmetry was defined as an absolute bilateral difference in measures when subtracting the breast density measures of the contralateral breast from the ipsilateral measures. Spearman9s correlations (rho) examined associations between breast density measures of the left and right breasts. To determine relationships between breast cancer risk factors (defined as categorical variables) and measures of bilateral breast density asymmetry, analysis of covariance (ANCOVA) models (PROC GLM) were used. Analyses were conducted at the per woman level using SAS. Probability values of Citation Format: Maeve Mullooly, Shaoqi Fan, Ruth M. Pfeiffer, Brian Sprague, Pamela M. Vacek, Donald L. Weaver, John A. Shepherd, Amir Pasha Mahmoudzadeh, Jeff Wang, Serghei Malkov, Jason M. Johnson, Sally D. Herschorn, Gretchen L. Gierach. Investigation of relationships between breast cancer risk factors and bilateral mammographic breast density asymmetry among women undergoing diagnostic image-guided breast biopsies [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr NG15.

Three-layer heterogeneous mammographic phantoms for Monte Carlo simulation of normalized glandular dose coefficients in mammography

Normalized glandular dose (DgN) coefficients obtained using homogeneous breast phantoms are commonly used in breast dosimetry for mammography. However, glandular tissue is heterogeneously distributed in the breast. This study aimed to construct three-layer heterogeneous mammographic phantoms (THEPs) to examine the effect of glandular distribution on DgN coefficient. Each layer of THEPs was set to 25%, 50%, or 75% glandular fraction to emulate heterogeneous glandular distribution. Monte Carlo simulation was performed to attain mean glandular dose (MGD) and air kerma at 22–36 kVp and W/Al, W/Rh, and W/Ag target–filter combinations. The heterogeneous DgN coefficient was calculated as functions of the mean glandular fraction (MGF), breast thickness, tube voltage, and half-value layer. At 50% MGF, the heterogeneous DgN coefficients for W/Al, W/Rh, and W/Ag differed by 40.3%, 36.7%, and 31.2%. At 9-cm breast thickness, the DgN values of superior and inferior glandular distributions were 25.4% higher and 29.2% lower than those of uniform distribution. The proposed THEPs can be integrated with conventional breast dosimetry to consider the heterogeneous glandular distribution in clinical practice.

Small Incision in Lower Posterior Axillary Wall Combining Multihole Drainage Technique for the Treatment of Axillary Bromhidrosis

Surgical excision of apocrine glands is an effective method for the treatment of bromhidrosis. However, common postoperative complications such as skin necrosis can result in prolonged healing and unsightly scars, which are mainly caused by surgical injuries and seroma or hematoma formation. We have improved the traditional surgical methods, in the hope that the new method can not only ensure the surgical effect, but also minimize the surgical trauma and postoperative complications. Forty-four patients with bromhidrosis were included. A 1-cm incision was made in the posterior wall of the lower axilla. Tissue scissors completely separated the skin from the subcutaneous tissue of glandular distribution. Iris scissors were used to trim subcutaneous glandular tissue, until there was only full-thickness skin left. Residual glandular tissue was removed with serrated edge curettage. After adequate irrigation and hemostasis, a drainage strip was placed in the incision. Then, we evenly divided the surgical area into 8 sections. In the center of each section, a draining hole was made. Of the 88 axillae, malodor was eradicated in 84 and considerably reduced in 4. Although 6 arms had temporary edema, and 10 axillae experienced superficial epidermal necrosis, no full-thickness skin necrosis was observed. Complications like hematoma, seroma, and infection were not present in all cases. All the scars of the incision and drainage holes were inconspicuous. The use of small incisions in the posterior axillary wall could accomplish sweat gland elimination and simultaneously provide excellent drainage. Combining this with porous drainage can effectively prevent hematoma, skin necrosis, and scar formation.

Inter-observer Reproducibility in the Pathologic Diagnosis of Gastric Intraepithelial Neoplasia and Early Carcinoma in Endoscopic Submucosal Dissection Specimens: A Multi-center Study.

PurposeThe diagnostic criteria of gastric intraepithelial neoplasia (IEN) are controversial across the world. We investigated how many discrepancies occur in the pathologic diagnosis of IEN and early gastric carcinoma in endoscopic submucosal dissection (ESD) specimens, and evaluated the reasons of the discordance. Materials and MethodsWe retrospectively reviewed 1,202 ESD specimens that were originally diagnosed as gastric IEN and early carcinoma at 12 institutions.ResultsThe final consensus diagnosis of carcinoma were 756 cases, which were originally 692 carcinomas (91.5%), 43 high-grade dysplasias (5.7%), 20 low-grade dysplasias (2.6%), and 1 others (0.1%), respectively. High- and low-grade dysplasia were finally made in 63 and 342 cases, respectively. The diagnostic concordance with the consensus diagnosis was the highest for carcinoma (91.5%), followed by low-grade dysplasia (86.3%), others (63.4%) and high-grade dysplasia (50.8%). The general kappa value was 0.83, indicating excellent concordance. The kappa values of individual institutions ranged from 0.74 to 1 and correlated with the proportion of carcinoma cases. The cases revised to a final diagnosis of carcinoma exhibited both architectural abnormalities and cytologic atypia. The main differential points between low- and high-grade dysplasias were the glandular distribution and glandular shape. Additional features such as the glandular axis, surface maturation, nuclear stratification and nuclear polarity were also important. ConclusionThe overall concordance of the diagnosis of gastric IEN and early carcinoma in ESD specimens was excellent. It correlated with the proportion of carcinoma cases, demonstrating that the diagnostic criteria for carcinoma are more reproducible than those for dysplasia.

Abstract ID: 225 Development of adjustable model breast using mammographic information for Monte Carlo simulation in nuclear medicine — Impact on dosimetry

For accurate estimation of the breast dose in nuclear medicine examinations, the development of an adjustable sizes model breast for Monte Carlo simulation is important. The development of the model breast for nuclear medicine studies is difficult because the size of the breast must be known. The purpose of this study is to develop the adjustable sizes model breast using mammographic information for Monte Carlo simulation in nuclear medicine and to investigate its impact on dosimetry using the SimDOSE simulation code [1] . This study constructed two sizes of ORNL phantoms with two radionuclides: 18F and 99mTc. The dimension of a breast phantom, a semi-oblate spheroid model, was established from the collected breast parameters of a cohort of patients in mammography [2] to provide a model breast allowing for changing sizes. Breast phantoms with various breast sizes, shapes, compositions, and the glandular distribution were created. The preliminary results showed the ratios of S-values of the breast ranged from 0.94 to 1.01 and the difference caused by breast shapes was insignificant. The organ dose of left and right breast may be considered separately due to in the dose difference between left and right breast. For different glandular distributions, the differences in S-values of the gland self-absorbed dose is about 5–8%. We conclude that the breast size has significant impacts and the glandular distribution has moderate impacts on the S-values of the breast, while the breast shape and compositions cause minor changes in the S-value. Therefore, this study provided the new method to assess the breast dose in Nuclear Medicine.

Abstract ID: 33 Monte Carlo evaluation of glandular dose estimates in X-ray breast computed tomography

A few groups have developed cone-beam breast computed tomography scanners dedicated to the breast (BCT) [1] , for breast cancer diagnosis. BCT is a 3D X-ray imaging technique, which aims at reducing the presence of the anatomical noise in X-ray breast images, due to the superposition of breast structures and tissues. The common metric for breast radiation dosimetry in BCT is the Mean Glandular Dose (MGD), i.e. the average absorbed dose in the glandular component of the breast tissue. The MGD is estimated on the basis of air kerma measurements, and normalized glandular dose coefficients (DgN) evaluated via Monte Carlo (MC) simulations [2] . In such a context, the breast is modeled as a homogenous mixture of glandular and adipose tissue embodied in a skin layer. We evaluated the DgN in BCT by modeling the breast as a heterogeneous mixture of adipose and glandular tissues. We realized an MC code based on GEANT4 toolkit simulating the acquisition setup and considering the interactions included in the standard electro-magnetic libraries. The MC code was previously validated vs. data from the AAPM Task Group 195, as well as vs. measured data. The dose was scored in locations inside a grid of cubic voxels designed using patient BCT scans provided by University of California Davis. The voxels were classified in adipose tissue, glandular tissue, skin tissue or air via an opportune segmentation algorithm. Such a voxellized phantom, with a real glandular distribution, was input in the MC code for estimating the MGD. This post-exam estimate was compared with the corresponding estimate evaluated before the exam using a homogeneous tissue mixture approximation. This project received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No. 692097 for the MaXIMA project: Three dimensional breast cancer models for X-ray imaging research.

Abstract ID: 203 Breast model validation for Monte Carlo evaluation of normalized glandular dose coefficients in mammography

In Monte Carlo simulations for estimation of normalized glandular dose coefficients (i.e. the ratio between the mean glandular dose (MGD) and incident air kerma at the breast upper surface), the radiosensitive breast tissue is modelled as a homogeneous mixture of adipose and glandular tissue. However, such an assumption has been shown to lead to an overestimation in MGD by an average of 30% [1] , [2] . This work aimed at comparing the homogeneous breast models proposed by different authors and in different quality assurance protocols to patient specific breast phantoms. To obtain these phantoms, uncompressed breast images were acquired with a CT scanner dedicated to the breast and segmented to classify each voxel into 4 categories: air, skin tissue, adipose tissue and glandular tissue. Then the compression which breasts undergo during a mammography exams was simulated via software in order to obtain 3D compressed patient specific breast phantoms which present an heterogeneous glandular distribution similar to that of the irradiated breast. The homogeneous breast phantom was simulated either with a 4-mm skin thickness (as adopted in the USA protocol), or with a 5-mm adipose layer simulating the skin and the subcutaneous adipose layer (as adopted in the EU protocol) or with a skin thickness of 1.45 mm (i.e. the skin thickness estimated from 3D breast images). A pre-validated Monte Carlo code based on GEANT4 toolkit ver. 10.00 [3] was employed to calculate the dose differences between the standard models and the patient specific breast phantom. This study provided an insight into possible bias of the standard models for breast dosimetry and an indication of new breast model for future normalized glandular dose calculations.

MAXIMA – A Horizon2020 project for increasing the research and innovation capacity of EU universities in the field of breast cancer modelling

Introduction In X-ray breast imaging, the availability of realistic three-dimensional computational and physical models of breast tumours and normal tissue structures (and corresponding histological evidences) would be a powerful tool in the hands of engineers, physicians and physicists for the development of new technologies and to validate computer tools for precise definition of the breast shapes, glandular tissue anatomical distribution, shape and type of breast cancer masses. Authorities may accept the results of computations as an alternative to tedious clinical studies. Aim In the frame of the EU Horizon2020 TWINN project three networking universities will cooperate towards an increase in the research and innovation capacity in breast modelling. The planned networking events should also contribute to education and training. Method Collaborative research will result in the development of more advanced computer-based breast cancer models. Together, the 3 partners have and allow access to several simulation platforms, phase contrast imaging, phase contrast tomosynthesis and state-of-the-art digital mammography. Proper validation and use of breast and lesion models for breast tomosynthesis and breast phase-contrast imaging is aimed for. Results During the kick-off meeting of the project, plans for educational workshops were made. Available tools and technologies have been listed and cooperation plans were made. The Ph.D. plans for the first 3 students have been discussed. Conclusion The created network will allow integration of the results of the ongoing research in the groups and will facilitate the research activities of all partners through a joint and mutually fruitful collaboration.

GEANT4 calculation of normalized glandular dose coefficients in computed tomography dedicated to the breast

Introduction Normalized glandular dose coefficients (gN CT )for computed tomography dedicated to the breast with a polychromatic X-ray source are available for estimating the mean glandular dose in a breast CT scan. However, a number of assumptions and simplifications are introduced in their derivation using Monte Carlo (MC) codes, both on breast geometry and on photon tracking and energy deposition details. Purpose To investigate, via MC simulations, four different factors which affect DgN CT calculation: (1) skin thickness, (2) electron tracking energy cutoff, (3) source position and (4) glandular tissue distribution. Materials and methods The MC code was developed using GEANT4. The breast was simulated as a cylindrical homogenous mixture of fat and glandular tissue. Skin thickness was varied from 1.45 to 4 mm. Monochromatic (8–80 keV) DgN CT have been calculated and the polychromatic DgN CT were computed by weighting them for typical X-ray tube spectra adopted for breast CT. A heterogeneous breast model as a mixture of adipose and randomly disposed glandular tissue voxels was investigated. Results Default GEANT4 electron energy cutoff leads to a DgN CT overestimation up to 1.6% at 60 keV. The skin thickness affects DgN CT values by about 1% (30–80 keV). DgN CT values calculated for a heterogeneous breast differ by 2% with respect to a homogeneous tissue mixture approximation. The X-ray source position also affects the DgN CT determinations, and setup-specific dose coefficients should be adopted. Conclusion Some factors which influence DgN CT MC calculations have been investigated and new polychromatic DgN CT coefficients have been computed in breast CT. Disclosure Nothing to declare.

Odorous secretions in anurans: morphological and functional assessment of serous glands as a source ofvolatile compounds in the skin of the treefrog Hypsiboas pulchellus (Amphibia: Anura: Hylidae).

Serous (granular or venom) glands occur in the skin of almost all species of adult amphibians, and are thought to be the source of a great diversity of chemical compounds. Despite recent advances in their chemistry, odorous volatile substances are compounds that have received less attention, and until now no study has attempted to associate histological data with the presence of these molecules in amphibians, or in any other vertebrate. Given the recent identification of 40 different volatile compounds from the skin secretions of H. pulchellus (a treefrog species that releases a strong odour when handled), we examined the structure, ultrastructure, histochemistry, and distribution of skin glands of this species. Histological analysis from six body regions reveals the presence of two types of glands that differ in their distribution. Mucous glands are homogeneously distributed, whereas serous glands are more numerous in the scapular region. Ultrastructural results indicate that electron-translucent vesicles observed within granules of serous glands are similar to those found in volatile-producing glands from insects and also with lipid vesicles from different organisms. Association among lipids and volatiles is also evidenced from chemical results, which indicate that at least some of the volatile components in H. pulchellus probably originate within the metabolism of fatty acids or the mevalonate pathway. As odorous secretions are often considered to be secreted under stress situations, the release of glandular content was assessed after pharmacological treatments, epinephrine administrated invivo and on skin explants, and through surface electrical stimulation. Serous glands responded to all treatments, generally through an obvious contraction of myoepithelial cells that surround their secretory portion. No response was observed in mucous glands. Considering these morpho-functional results, along with previous identification of volatiles from H. pulchellus and H. riojanus after electrical stimulation, we suggest that the electron-translucent inclusions found within the granules of serous glands likely are the store sites of volatile compounds and/or their precursors. Histochemical and glandular distribution analyses in five other species of frogs of the hylid tribe Cophomantini, revealed a high lipid content in all the species, whereas a heterogeneous distribution of serous glands is only observed in species of the H. pulchellus group. The distribution pattern of serous glands in members of this species group, and the odorous volatile secretions are probably related to defensive functions.

Breast dose in mammography is about 30% lower when realistic heterogeneous glandular distributions are considered.

Current dosimetry methods in mammography assume that the breast is comprised of a homogeneous mixture of glandular and adipose tissues. Three-dimensional (3D) dedicated breast CT (bCT) data sets were used previously to assess the complex anatomical structure within the breast, characterizing the statistical distribution of glandular tissue in the breast. The purpose of this work was to investigate the effect of bCT-derived heterogeneous glandular distributions on dosimetry in mammography. bCT-derived breast diameters, volumes, and 3D fibroglandular distributions were used to design realistic compressed breast models comprised of heterogeneous distributions of glandular tissue. The bCT-derived glandular distributions were fit to biGaussian functions and used as probability density maps to assign the density distributions within compressed breast models. The MCNPX 2.6.0 Monte Carlo code was used to estimate monoenergetic normalized mean glandular dose "DgN(E)" values in mammography geometry. The DgN(E) values were then weighted by typical mammography x-ray spectra to determine polyenergetic DgN (pDgN) coefficients for heterogeneous (pDgNhetero) and homogeneous (pDgNhomo) cases. The dependence of estimated pDgN values on phantom size, volumetric glandular fraction (VGF), x-ray technique factors, and location of the heterogeneous glandular distributions was investigated. The pDgNhetero coefficients were on average 35.3% (SD, 4.1) and 24.2% (SD, 3.0) lower than the pDgNhomo coefficients for the Mo-Mo and W-Rh x-ray spectra, respectively, across all phantom sizes and VGFs when the glandular distributions were centered within the breast phantom in the coronal plane. At constant breast size, increasing VGF from 7.3% to 19.1% lead to a reduction in pDgNhetero relative to pDgNhomo of 23.6%-27.4% for a W-Rh spectrum. Displacement of the glandular distribution, at a distance equal to 10% of the compressed breast width in the superior and inferior directions, resulted in a 37.3% and a -26.6% change in the pDgNhetero coefficient, respectively, relative to the centered distribution for the Mo-Mo spectrum. Lateral displacement of the glandular distribution, at a distance equal to 10% of the compressed breast width, resulted in a 1.5% change in the pDgNhetero coefficient relative to the centered distribution for the W-Rh spectrum. Introducing bCT-derived heterogeneous glandular distributions into mammography phantom design resulted in decreased glandular dose relative to the widely used homogeneous assumption. A homogeneous distribution overestimates the amount of glandular tissue near the entrant surface of the breast, where dose deposition is exponentially higher. While these findings are based on clinically measured distributions of glandular tissue using a large cohort of women, future work is required to improve the classification of glandular distributions based on breast size and overall glandular fraction.

Reduced GLP-1R expression in gastric glands of patients with type 2 diabetes mellitus.

The incretin effect is reduced in type 2 diabetes mellitus (T2DM) patients. Whether the impaired function of the enteropancreatic axis in these patients is due to defective GLP-1 receptor (GLP-1R) expression in extrapancreatic target organs is not known. To compare the GLP-1R expression and distribution in gastric mucosa biopsies of patients with (n =22) and without (n =22) T2DM referred for routine esophagogastroduodenoscopies. GLP-1R mRNA levels were estimated by real-time PCR. The intensity of GLP-1R immunostaining, frequency, and types of glandular cells bearing GLP-1R and their glandular distribution in different stomach mucosa regions were evaluated by immunohistochemical morphological semiquantitative and quantitative analysis. Mean mRNA GLP-1R levels were significantly reduced in patients with T2DM compared with nondiabetic patients (P < .02). Immunohistochemical analysis revealed that the reduced GLP-1R expression in T2DM patients was due to a decreased intensity of immunostaining (P < .01). The number of glandular GLP-1R-bearing cells in both body and antrum mucosa was decreased in T2DM patients. Most notably, the frequency of GLP-1R immunoreactive acid-secreting parietal cells was reduced in the neck area of the gastric principal glands of T2DM patients (P < .01). No correlation was found between the reduced GLP-1R expression and clinical parameters including body mass index, age, glycosylated hemoglobin, and disease duration. This is the first evidence of reduced GLP-1R expression in gastric glands of T2DM patients. These data demonstrate that the defective function of the incretin axis in T2DM may also result from decreased GLP-1R expression in its extrapancreatic target organs.

TU-F-18C-05: Evaluation of a Method to Calculate Patient-Oriented MGD Coefficients Using Estimates of Glandular Tissue Distribution

Purpose: Evaluate mammographic mean glandular dose (MGD) coefficients for particular known tissue distributions using a novel formalism that incorporates the effect of the heterogeneous glandular tissue distribution, by comparing them with MGD coefficients derived from the corresponding anthropomorphic computer breast phantom. Methods: MGD coefficients were obtained using MCNP5 simulations with the currently used homogeneous assumption and the heterogeneously-layered breast (HLB) geometry and compared against those from the computer phantom (ground truth). The tissue distribution for the HLB geometry was estimated using glandularity map image pairs corrected for the presence of non-glandular fibrous tissue. Heterogeneity of tissue distribution was quantified using the glandular tissue distribution index, Idist. The phantom had 5 cm compressed breast thickness (MLO and CC views) and 29% whole breast glandular percentage. Results: Differences as high as 116% were found between the MGD coefficients with the homogeneous breast core assumption and those from the corresponding ground truth. Higher differences were found for cases with more heterogeneous distribution of glandular tissue. The Idist for all cases was in the [−0.8{sup −}+0.3] range. The use of the methods presented in this work results in better agreement with ground truth with an improvement as high as 105 pp. The decrease inmore » difference across all phantom cases was in the [9{sup −}105] pp range, dependent on the distribution of glandular tissue and was larger for the cases with the highest Idist values. Conclusion: Our results suggest that the use of corrected glandularity image pairs, as well as the HLB geometry, improves the estimates of MGD conversion coefficients by accounting for the distribution of glandular tissue within the breast. The accuracy of this approach with respect to ground truth is highly dependent on the particular glandular tissue distribution studied. Predrag Bakic discloses current funding from NIH, NSF, and DoD, former funding from Real Time Tomography, LLC and a current research collaboration with Barco and Hologic.« less

GLP-1 Receptor Is Expressed in Human Stomach Mucosa

The stomach is a target organ of the incretin hormone glucagon-like peptide-1 (GLP-1). However, the cellular expression and glandular distribution of its receptor (GLP-1R) in human gastric mucosa are not known. We determined the expression of GLP-1R in different regions of human stomach mucosa and its specific cellular association and distribution within gastric glands. Tissue samples from stomach body and antrum were obtained from 20 patients during routine esophagogastroduodenoscopy. mRNA encoding GLP-1R protein expression was evaluated by RT-PCR. Determination of cell types bearing GLP-1R, their localization, and their frequency in gastric glands in different gastric regions were estimated by immunohistochemical morphological analysis. Levels of GLP-1R mRNA were similar in body and antrum. GLP-1R immunoreactivity was found throughout the gastric mucosa in various types of glandular cells. The highest frequency of GLP-1R immunoreactive cells was found in the neck area of the principal glands in cells morphologically identified as parietal cells. GLP-1R immunostaining was also found on enteroendocrine-like cells in the pyloric glands. This study provides the first description of GLP-1R expression in human gastric glands and its specific cellular association. Our data suggest that GLP-1 may act directly on the gastric mucosa to modulate its complex functions.

WE-G-103-08: Retrospective Determination of Personalized Mean Glandular Dose Coefficients for Conventional Mammography Using Heterogeneously-Layered Breast Models

Purpose: The heterogeneous distribution of the glandular tissue is overlooked in calculations of mean glandular dose (MGD). In this work, we introduce a methodology for the calculation of patient‐oriented dose conversion coefficients. In addition, we provide an empirical relationship to use for the estimation of these coefficients in a clinical setting. Methods: Breast density assessment software was used to obtain the breast density maps from conventional mammography four‐view sets of images in a group of 31 patients. The glandular tissue distribution for each breast was estimated from the breast density maps using the Mammography‐Image Based (MIB) method presented in this work. The corresponding patient‐oriented dose conversion coefficients (DgN‐HLB) were determined using Monte Carlo methods and a Heterogeneously‐Layered Breast (HLB) geometry. This geometry models the breast core as composed of layers with different glandular percentage, as opposed to a homogeneous breast core. The DgN‐HLB were compared to the corresponding dose conversion coefficients based on a homogeneous core breast geometry (DgN). Results: Differences as high as 49% between the DgN‐HLB and their corresponding DgN were found. The difference between DgN and DgN‐HLB was found to have a linear relationship with the glandular distribution index (I_dist) calculated in this work. This relationship was used to make a patient‐specific correction to the DgN (k_dist) that allows for estimations of DgN‐HLB, without the use of patient‐based Monte Carlo simulations. Both HLB‐based approaches agree within 10.5%. Conclusion: We have developed a method to obtain estimations of the glandular tissue distribution from conventional mammography images using their corresponding breast density maps. Our work provides a methodology to incorporate anatomical information in the calculation of patient‐oriented MGD, thereby overcoming one of the known limitations of the currently used mammography dosimetry methods.

Tissue Expression of Glandular Kallikrein and Its Response to 17 β-estradiol in the Acclimatized Carp

Cyprinus carpio skeletal muscle kallikrein was isolated to apparent homogeneity, and a polyclonal antiserum against the purified protein was generated. Glandular kallikrein expression and tissue distribution were assessed using both Western blots and immunohistochemistry. A 39-kDa protein was detected in skeletal muscle, the gill, kidney, and pituitary gland, where an additional 72-kDa immunoreactive band was observed. Immunohistochemistry revealed immunoreactive kallikrein in the intermuscle tissue, epithelial gill cells, apical portion of distal and proximal tubular cells in the kidney, mucus and epithelial cells of the skin, intestinal tube, and prolactin-producing cells of the pituitary gland. In addition, the effect of 17beta-estradiol on kallikrein expression was analyzed in three different tissues of winter- and summer-acclimatized male carps. A 2.5-fold (p<0.05) increase in kallikrein immunoreactivity due to estrogen treatment was observed in winter-acclimatized carp muscle, but not in summer-acclimatized fish. In contrast, the gill responded differently, since a 2-fold (p<0.05) increase was found only in summer-acclimatized carps. Kallikrein immunoreactivity in the kidney increased both in summer- (2.5 fold) and in winter-acclimatized carps (1.5 fold). The signals obtained demonstrate the existence of tissue-specific variable responses to estrogen treatment in vivo, between winter and summer-acclimatized carp.